The long-term objective of this project is to develop a comprehensive understanding of the pathophysiologic mechanisms involved in collagen-induced arthritis in rodents and to determine if similar mechanisms are involved in human arthritis. Previous studies have suggested the importance of anti-native type II collagen antibodies in arthritis in rats. This project will localize the deposition of antibody in acute arthritis by immunofluorescence and autoradiography. The role of cell-mediated reactions will be investigated by cell transfer experiments and by isolating and characterizing cells from arthritic joints. Mice also are susceptible to arthritis and will be investigated to determine if similar mechanisms are responsible for arthritis in mice. Genetic influences of arthritis susceptibility in mice will be determined in two different susceptible strains, by serum transfer between high antibody forming arthritic and nonarthritic strains, and by immunization of auto-immune strains. The precise epitope on native type II collagen recognized by antibodies capable of inducing arthritis will be identified. Since collagen autoimmunity has also been described in human arthritis, fully understanding the animal model should permit well defined studies of human arthritis with the aim of identifying similar reactions. In particular if antibodies of the same specificity as those critical to collagen-induced arthritis are present in human arthritis, it would strengthen the hypothesis that collagen autoimmunity is of pathologenic importance in human arthritis.